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Background: Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome-wide association study (GWAS)., Methods: We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole-genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity., Results: The GWAS identified five non-coding variants on chromosome 20 with a p-value <5.0 × 10 -8 . For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions., Conclusions: Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients., Significance Statement: This genome-wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Primary squamous cell carcinoma (SCC) can originate in different parts of the body, including the head, neck, lung, bronchus, cervix uteri, esophagus, and cardia, and subsequently metastasize to the stomach. Primary gastric squamous cell carcinoma (GSCC) is a rare disease. To better understand GSCC, we present the case of a 72-year-old woman with a primary GSCC. A chest and abdominal CT scan highlighted a 36×26 mm mass with a 41 mm longitudinal diameter, which included the origin of the celiac tripod. The disease appeared to originate exophytically from the gastric wall. An ultrasound-endoscopy showed a hypoechoic formation with not well-defined margins measuring 40×30 mm involving the origin of the celiac tripod, about 10 mm from the gastric wall. An endoscopic fine-needle aspiration showed a poorly differentiated carcinoma. A PET/CT scan showed a hyperaccumulation of the known expansive formation at the celiac tripod (SUV 11.9) without specific cleavage planes from the stomach. A gastroscopy showed a regular esophagus and an absence of gastric protruding lesions. In the subcardial area, on the posterior wall, there was a slightly raised sub-centimetric area covered by bleeding mucosa where the biopsy had been performed. The pathological report showed chronic gastritis. An eco-endoscopy confirmed a hypoechoic neoformation measuring 30×40 mm that appeared to originate from the muscular layer of the gastric wall. The biopsy report was positive for broad-spectrum cytokeratins (AE1/AE3), CK5/6/7, p40, p63 and negative for CK20, PAS, TTF-1, anti-smooth muscle actin, CD45 (LCA), ERG, and S100. The clinical picture suggested poorly differentiated carcinoma with squamous differentiation. We analyzed the main classifications of GSCC cases and compared their characteristics. It is clear that to have an appropriate definition of GSCC, well-defined diagnostic criteria are needed. Currently, there is no consensus. For practical purposes, it would be better to include a panel of CK and p40 to distinguish GSCC from adenocarcinoma. A GSCC outside the mucosa is not rare and could be a true entity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Monti, Limarzi, Oboldi, Sbrancia, Pallotti, Miserocchi, Ghini, Zanuccoli, Cagnazzo and Frassineti.)

Aim and Objectives: To present our experience of a nursing telephone consultation service, describing patient and caregiver requests, and outlining ensuing nursing or medical interventions., Background: Recently, there has been an increase in the use of telephone consultation for cancer patients. However, there is still limited data on the characteristics of this type of service and on the nature of the interventions carried out., Design and Methods: In this observational retrospective study, we evaluated the phone calls made over a 6-month period by patients or caregivers to the early palliative care team of a cancer institute. Information regarding telephone calls (frequency, reason and management) was systematically collected by a nursing case manager. The study complies with the STROBE checklist File S1., Results: 171 patients used the service, for a total of 323 phone calls. The majority (80.8%) were from patients followed at the outpatient clinic and the most common requests were for pain management (38.4%) and for updates on the clinical situation (23.8%). Other frequent requests were for medication management (18.9%) and scheduling (18.3%). 210 of the 323 phone calls were handled by the nurse, while 22 were managed in collaboration with a physician. An 87.6% effectiveness in telephone management was observed., Conclusion: The overall use of the phone service was higher for early palliative care patients. The majority of phone calls were effectively handled by the nursing case manager., Relevance to Clinical Practice: An effective and feasible nurse-led telephone follow-up of early palliative care patients with advanced cancer could improve their care experience. Specifically, it could impact on patients and families improving quality of life and symptom control securing access to timely care without travel or additional cost.It can also improve continuity of care, adherence to oncological treatments and minimise acute care visits., (© 2022 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Introduction: It is estimated that of those who die in high-income countries, 69%-82% would benefit from palliative care with a high prevalence of advanced chronic conditions and limited life prognosis. A positive response to these challenges would consist of integrating the palliative approach into all healthcare settings, for patients with all types of advanced medical conditions, although poor clinician awareness and the difficulty of applying criteria to identify patients in need still pose significant barriers. The aim of this project is to investigate whether the combined use of the NECPAL CCOMS-ICO and Palliative Prognostic (PaP) Score tools offers valuable screening methods to identify patients suffering from advanced chronic disease with limited life prognosis and likely to need palliative care, such as cancer, chronic renal or chronic respiratory failure., Methods and Analysis: This multicentre prospective observational study includes three patient populations: 100 patients with cancer, 50 patients with chronic renal failure and 50 patients with chronic pulmonary failure. All patients will be treated and monitored according to local clinical practice, with no additional procedures/patient visits compared with routine clinical practice. The following data will be collected for each patient: demographic variables, NECPAL CCOMS-ICO questionnaire, PaP Score evaluation, Palliative Performance Scale, Edmonton Symptom Assessment System, Eastern Cooperative Oncology Group Performance Status and data concerning the underlying disease, in order to verify the correlation of the two tools (PaP and NECPAL CCOMS-ICO) with patient status and statistical analysis., Ethics and Dissemination: The study was approved by local ethics committees and written informed consent was obtained from the patient. Findings will be disseminated through typical academic routes including poster/paper presentations at national and international conferences and academic institutes, and through publication in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: On the basis of substantial evidence demonstrate that palliative care combined with standard care improves patient, caregiver, and society outcomes, we have developed a new healthcare model called radiotherapy and palliative care (RaP) outpatient clinic were a radiation oncologist and a palliative care physician make a joint evaluation of advanced cancer patients., Methods: We performed a monocentric observational cohort study on advanced cancer patients referred for evaluation at the RaP outpatient clinic. Measures of quality of care were carried out., Results: Between April 2016 and April 2018, 287 joint evaluations were performed and 260 patients were evaluated. The primary tumor was lung in 31.9% of cases. One hundred fifty (52.3%) evaluations resulted in an indication for palliative radiotherapy treatment. In 57.6% of cases was used a single dose fraction of radiotherapy (8 Gy). All the irradiated cohort completed the palliative radiotherapy treatment. An 8% of irradiated patients received the palliative radiotherapy treatment in the last 30 days of life. A total of 80% of RaP patients received palliative care assistance until the end of life., Conclusion: At the first descriptive analysis, the radiotherapy and palliative care model seem to respond to the need of multidisciplinary approach in order to obtain an improvement on quality of care for advanced cancer patients., (© 2023. The Author(s).)

Background: Prognostication can be used within a tailored decision-making process to achieve a more personalized approach to the care of patients with cancer. This prospective observational study evaluated the accuracy of the Palliative Prognostic score (PaP score) to predict survival in patients identified by oncologists as candidates for palliative radiotherapy (PRT). We also studied interrater variability for the clinical prediction of survival and PaP scores and assessed the accuracy of the Survival Prediction Score (SPS) and TEACHH score., Materials and Methods: Consecutive patients were enrolled at first access to our Radiotherapy and Palliative Care Outpatient Clinic. The discriminating ability of the prognostic models was assessed using Harrell's C index, and the corresponding 95% confidence intervals (95% CI) were obtained by bootstrapping., Results: In total, 255 patients with metastatic cancer were evaluated, and 123 (48.2%) were selected for PRT, all of whom completed treatment without interruption. Then, 10.6% of the irradiated patients who died underwent treatment within the last 30 days of life. The PaP score showed an accuracy of 74.8 (95% CI, 69.5-80.1) for radiation oncologist (RO) and 80.7 (95% CI, 75.9-85.5) for palliative care physician (PCP) in predicting 30-day survival. The accuracy of TEACHH was 76.1 (95% CI, 70.9-81.3) and 64.7 (95% CI, 58.8-70.6) for RO and PCP, respectively, and the accuracy of SPS was 70 (95% CI, 64.4-75.6) and 72.8 (95% CI, 67.3-78.3)., Conclusion: Accurate prognostication can identify candidates for low-fraction PRT during the last days of life who are more likely to complete the planned treatment without interruption.All the scores showed good discriminating capacity; the PaP had the higher accuracy, especially when used in a multidisciplinary way., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maltoni, Scarpi, Dall’Agata, Micheletti, Pallotti, Pieri, Ricci, Romeo, Tenti, Tontini and Rossi.)

Aim: The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none., Methods: Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of <60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60., Results: Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively., Conclusion: Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance., (© The Author(s) 2022. Published by Oxford University Press.)

Introduction: New treatments have improved the overall survival of patients with multiple myeloma (MM). At diagnosis and during the course of the disease, patients often report pain and other symptoms. Given the long disease trajectory, psychological and social issues are also frequent. Recently, the potential usefulness of early palliative care (EPC) was hypothesized in the area of hematology. We conducted a retrospective analysis of patients with MM referred to our institute for a palliative care (PC) consultation between January 2017 and June 2020. Our aim was to evaluate the main reasons (pain or other clinical symptoms) for the referral for a first PC consultation., Methods: We examined the main reasons for the first PC consultation, the number of PC consultations carried out, and the period of time between diagnosis, first and subsequent PC visits, and death. We also recorded information on the type of pain experienced and the treatments administered., Results: Of the 325 patients with MM followed at our hematology unit during the study period, 43 were referred for a PC consultation (39 for pain management and 4 to determine the most appropriate care setting (hospice or palliative homecare service)). Nineteen (44.2%) of the 43 patients reported other symptoms in addition to pain. The median time between MM diagnosis and the first PC consultation was 473 days. Fifteen patients died, with a median 332 days between the first PC visit and death., Conclusion: Randomized studies on MM involving larger patient populations with access to EPC are needed to identify an effective clinical model to improve the management of patients with MM., (© 2021. The Author(s).)